Antibodies to nucleic acids are important diagnostically and pathogenetically in systematic lupus. The production of these antibodies is in part controlled by the X-chromosome through regulation of maturation of B cells destined to make IgM antibodies to nucleic acids. Sex chromosomes indirectly influence the magnitude to auto-antibody production through sex hormones: male sex hormones suppress the production of anti-nucleic acid antibodies. Antibodies to transfer RNA are produced by patients with SLE; these cross-react with viral nucleic acids. Subpopulations of patients have specific auto-antibodies.